Effects of single-point mutations on translocation of non-interacting heteropolymer protein chains

Abstract

We analyse the role of single-point mutations on the translocation of heteropolymer protein chains with helical folding. We propose a statistical mechanics model that computes the equilibrium partition function of a given protein by incorporating experimental helix propensities of amino acids. From that we evaluate the free energy barrier for translocation and the average translocation time for single-point protein mutants and compared with wild-type proteins used as reference. In our calculations, single-point mutations that increase energy of the folded state in increase the energy barrier for translocation up to , , in consequence, the translocation time undergoes variations between and with the largest variations associated to substitutions of amino acids glycine and proline by alanine. In fact, substitutions of amino acids with the lowest helix propensities by amino acids with the largest helix propensities induced the largest mutational effects. These results indicate that effects of single-point mutations become evident when mutations increase energy of the folded state at least in . Our model predicts translocation time delays for proline to alanine single-point mutations which agree with deficiencies of protein translocation observed recently in experiments.